Treatment with the α-glucosidase inhibitor miglitol from the preonset stage in Otsuka Long-Evans Tokushima Fatty rats improves glycemic control and reduces the expression of inflammatory cytokine genes in peripheral leukocytes

Abstract

Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of type 2 diabetes mellitus, exhibit chronic and slowly progressive hyperglycemia with obesity. In this study, we examined whether dietary supplementation with the α-glucosidase inhibitor miglitol from the preonset stage improves glycemic control and reduces the gene expression of inflammatory cytokines in peripheral leukocytes. The OLETF rats were fed a control diet or a diet containing 800 ppm miglitol (miglitol diet) for 40 weeks from 5 weeks of age (preonset stage). We determined nonfasting blood glucose, blood 1,5-anhydroglucitol, and messenger RNA levels of inflammatory cytokines in peripheral leukocytes in these rats. Nonfasting blood glucose concentrations gradually increased in OLETF rats fed the control diet, with significant increases at weeks 28 and 40 compared with week 0. In contrast, nonfasting blood glucose levels did not increase in miglitol-treated rats during the experimental period. Miglitol-treated rats had lower nonfasting blood glucose levels and higher 1,5-anhydroglucitol levels, a marker for glucose fluctuations, at week 40 than control rats. The gene expression of inflammatory cytokines including interleukin-6, tumor necrosis factor-α, and interferon-γ in peripheral leukocytes gradually increased during the development of diabetes in control rats, but not in miglitol-treated rats. Our results suggest that dietary supplementation with miglitol from the preonset stage in OLETF rats improves glycemic control and reduces gene expression of cytokines related to inflammation in peripheral leukocytes.